Surrogate endpoint

In clinical trials, a surrogate endpoint (also called a surrogate measure or surrogate marker) is a measure of effect of a specific treatment that may correlate with a realclinical endpoint but does not necessarily have a guaranteed relationship. The National Institutes of Health (USA) defines surrogate endpoint as "a biomarker intended to substitute for a clinical endpoint".

Surrogate markers are used when the primary endpoint is undesired (e.g., death), or when the number of events is very small, thus making it impractical to conduct a clinical trial to gather a statistically significant number of endpoints. The FDA and other regulatory agencies will often accept evidence from clinical trials that show a direct clinical benefit to surrogate markers.

Surrogate endpoints can be obtained from different modalities, such as, behavioural or cognitive scores, or biomarkers from Electroencephalography (qEEG), MRI, PET, or biochemical biomarkers.

A correlate does not make a surrogate. It is a common misconception that if an outcome is a correlate (that is, correlated with the true clinical outcome) it can be used as a valid surrogate endpoint (that is, a replacement for the true clinical outcome). However, proper justification for such replacement requires that the effect of the intervention on the surrogate endpoint predicts the effect on the clinical outcome: a much stronger condition than correlation. In this context, the term Prentice criteria is used.

The most commonly used approach to validate a surrogate endpoint is to conduct a meta-analysis of randomized clinical trials in which the surrogate and the true endpoints are measured.

A surrogate endpoint of a clinical trial is a laboratory measurement or a physical sign used as a substitute for a clinically meaningful endpoint that measures directly how a patient feels, functions or survives. Changes induced by a therapy on a surrogate endpoint are expected to reflect changes in a clinically meaningful endpoint.